We have previously shown that prostaglandins of the E series (PGE) prevent the development of immune complex glomerulonephritis (GN). The model of GN has been developed in our laboratory and is produced by the daily injection of a foreign protein, apoferritin. Mice receiving apoferritin develop proteinuria and a diffuse proliferative glomerulonephritis with peripheral granular deposition of IgG by immunofluorescence. Administration of pharmacologic doses of PGE prevents the development of proteinuria, inhibits glomerular damage, and reduces immune complex deposition. The aims of this proposal are: 1) to identify any alterations in humoral immune response induced by PGE2; 2) to identify any alterations in cellular immune response with PGE2 treatment; 3) to determine if administration of PGE2 after the onset of GN reduces glomerular damage; and 4) to determine if PGE2 alters the reticuloendothelial system (RES) handling of immune complexes. The humoral immune response will be examined at intervals in mice receiving apoferritin or apoferritin plus PGE2 in terms of anti-apoferritin antibody, serum immunoglobulin levels, circulating immune complexes, and plaque forming cell response (PFC) to apoferritin. The cellular immune response will be studied by determing the effect of spleen cells from mice receiving PGE2 on the de novo generation of antibody producing cells in vitro using spleen cells from normal mice. These reconstitution experiments will look for specific suppressor cells by using subpopulations of T cells, B cells and macrophages. The possibility that PGE2 is activating a splenic suppressor cell will also be studied by passive transfer of spleen cells from mice receiving PGE2 to mice receiving apoferritin. The ability of PGE2 to alter established GN will be studied by beginning administration of PGE2 at various intervals after the onset of apoferritin injections. The RES handling of complexes will be examined by determining if a difference in the clearance rate of colloidal carbon or aggregated IgG is induced by PGE2. The experiments will provide a significant advance in our knowledge about PG regulation of immune response and the role of PG in preventing the development of GN. This knowledge may lead to effective, rational therapy of human GN.